Cancer refers to an organism's abnormal cellular proliferation, and these abnormally proliferated cells may invade other parts of the organism. There are many factors that cause cancer, such as obesity, poor nutrition, insufficient exercise, alcohol, infection, radiation, environmental pollution factors, genetics, viral infections and so on.
Because of the fast pace of today's society, pollution, and more sedentary lifestyles, cancer has become a major cause of death in many countries, especially in developed countries. People of every age and stage may suffer from cancer during their lives. Because DNA damage is one of the reasons that causes cancer, and because that may increase as people age, the risk of cancer is also increasing.
Cancer may be treated with surgery, chemotherapy, radiotherapy, immunotherapy, monoclonal antibody therapy and so on. The treatment method depends on the position of any tumor, malignancy, progress, patient's condition and so on.
Heat shock proteins (Hsp) include a certain group of highly conserved stress proteins which have attracted attention due to their overexpression in cancer tissues. Overexpression of these Hsp proteins is related to metastatic potential, resistance to chemotherapy and poor prognosis. Hsp proteins are named depending on their molecular weight (such as Hsp60, Hsp70 and Hsp90) and among the most studied protein is Hsp90. This protein is the most prominent member of the highly abundant chaperone proteins and it is essential for folding nascent polypeptide to control the activity, stability and protein sorting. Hsp90 has been identified as a promising drug target for cancer treatment, because it can stabilize and activate a variety of survival proteins to maintain cancer phenotype and help cancer cells to overcome multiple environmental stresses. There is considerable interest in developing potential Hsp90 inhibitors with a much simpler rationale through the depletion of oncogenic Hsp90 clients. Tanespimycin (17-allylamine-17-demethoxygeldanamycin, 17-AAG), the first Hsp90 inhibitor, was found to bind to the N-terminal regulatory pocket of Hsp90 and thus inhibiting its function. However, further clinical development of 17-AAG was halted because of poor solubility, limited bioavailability, and unacceptable hepatotoxicity.
Another important group of proteins, topoisomerases (Topo), have also attracted attention due to their crucial role in cell survival and replication. Topoisomerases are classified into two main classes: topoisomerase I (Topo I) and topoisomerase II (Topo II), wherein Topoisomerase II is composed of two isoforms, α and β, which share highly similar amino acid sequence (up to 70%). Topo IIα is essential for the survival of proliferating cells and can distinguish the handedness of DNA supercoils during relaxation reactions. However, Topo IIB is dispensable at the cellular level. Topo II disentangle topological problems, which regulate DNA replication, transcription and chromosome segregation, and processes related to tumorigenesis. Inhibition of Topo II activity is one of the current therapeutic protocols targeting several cancers including lung, breast, lymphomas, testicular and sarcomas. The inhibition of Topo II activity is achieved either with poisons, which interfere with the topoisomerase-DNA complex or inhibitors, which suppress the catalytic turnover. Despite the effectiveness of Topo II poisons as anticancer drugs, they can trigger chromosomal breaks leading to secondary leukemogenesis.
Although there are techniques and research for treating cancer described above or not described herein, scientists still endeavor to find novel and efficient techniques, drugs and therapies for cancer treatments.
It is therefore the Applicant's attempt to deal with the above limitations in the prior art.